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Öğe Bisphosphonate (Zoledronic Acid) Associated Adverse Events: Single Center Experience(Akad Doktorlar Yayinevi, 2010) Kucukzeybek, Yuksel; Gorumlu, Gurbuz; Cengiz, Ercument; Erten, Cigdem; Karaca, Burcak; Gul, M. Kemal; Karabulut, Bulent; Sanli, Ulus A.; Uslu, RuchanZoledronic acid is an efficacy-proven bisphosphonate used in the patients who develop bone metastasis. In our study, we planned to evaluate side effects occurring in the patients who receive zoledronic acid. The records of a total of 5.482 patients diagnosed with solid tumor who were admitted to oncology out-patients' clinic between January 2001 and January 2007 were scanned. It was found that 256 patients received zoledronic acid. Zoledronic acid is administered in 4 mg doses for a period of 15 minutes as intravenous infusion once in 21/28 days. Side effects such as hypocalcemia, symptomatic hypocalcemia, impairment in renal functions and osteonecrosis of the jaw, were evaluated retrospectively. Zoledronic acid was administered due to bone metastasis in 248 patients, malign hypercalcemia in 6 patients and ostoporosis in 2 patients. Four patients (1.5%) were diagnosed with jaw osteonecrosis, 22 patients (8.5%) were diagnosed with hypocalcemia, 19 patients (7.4%) were diagnosed with impairment in renal functions, and 2 patients were (0.7%) diagnosed with symptomatic hypocalcemia. Zoledronic acid is a bisphosphonate which has been proven to reduce complications which may develop depending on the bone metastasis, such as pathological fracture, spinal chord impression andhypercalcemia. On the other hand, side effects may occur in the patients receiving zoledronic acid. It will be appropriate to inform the patients who are planned to start administering zoledronic acid of the benefits to be obtained and the side effects to take place.Öğe The clinical and pathological features of 133 colorectal cancer patients with brain metastasis: a multicenter retrospective analysis of the Gastrointestinal Tumors Working Committee of the Turkish Oncology Group (TOG)(Humana Press Inc, 2014) Tanriverdi, Ozgur; Kaytan-Saglam, Esra; Ulger, Sukran; Bayoglu, Ibrahim Vedat; Turker, Ibrahim; Ozturk-Topcu, Turkan; Cokmert, Suna; Turhal, Serdar; Oktay, Esin; Karabulut, Bulent; Kilic, Diclehan; Kucukzeybek, Yuksel; Oksuzoglu, Berna; Meydan, Nezih; Kaya, Vildan; Akman, Tulay; Ibis, Kamuran; Saynak, Mert; Sen, Cenk Ahmet; Uysal-Sonmez, Ozlem; Pilanci, Kezban Nur; Demir, Gokhan; Saglam, Sezer; Kocar, Muharrem; Menekse, Serkan; Goksel, Gamze; Yapar-Taskoylu, Burcu; Yaren, Arzu; Uyeturk, Ummugul; Avci, Nilufer; Denizli, Bengu; Ilis-Temiz, EsraBrain metastasis in colorectal cancer is highly rare. In the present study, we aimed to determine the frequency of brain metastasis in colorectal cancer patients and to establish prognostic characteristics of colorectal cancer patients with brain metastasis. In this cross-sectional study, the medical files of colorectal cancer patients with brain metastases who were definitely diagnosed by histopathologically were retrospectively reviewed. Brain metastasis was detected in 2.7 % (n = 133) of 4,864 colorectal cancer patients. The majority of cases were male (53 %), older than 65 years (59 %), with rectum cancer (56 %), a poorly differentiated tumor (70 %); had adenocarcinoma histology (97 %), and metachronous metastasis (86 %); received chemotherapy at least once for metastatic disease before brain metastasis developed (72 %), had progression with lung metastasis before (51 %), and 26 % (n = 31) of patients with extracranial disease at time the diagnosis of brain metastasis had both lung and bone metastases. The mean follow-up duration was 51 months (range 5-92), and the mean survival was 25.8 months (95 % CI 20.4-29.3). Overall survival rates were 81 % in the first year, 42.3 % in the third year, and 15.7 % in the fifth year. In multiple variable analysis, the most important independent risk factor for overall survival was determined as the presence of lung metastasis (HR 1.43, 95 % CI 1.27-4.14; P = 0.012). Brain metastasis develops late in the period of colorectal cancer and prognosis in these patients is poor. However, early screening of brain metastases in patients with lung metastasis may improve survival outcomes with new treatment modalities.Öğe Docetaxel plus platinum combination regimen in locally advanced or metastatic head and neck cancer(Oxford Univ Press, 2006) Kucukzeybek, Yuksel; Gorumlu, Gurbuz; Karabulut, Bulent; Uslu, Ruchan; Sanli, Ulus A.; Goker, ErdemÖğe Enhanced cytotoxicity and apoptosis by thymoquinone in combination with zoledronic acid in hormone- and drug-resistant prostate cancer cell lines(Imprimatur Publications, 2014) Dirican, Ahmet; Erten, Cigdem; Atmaca, Harika; Bozkurt, Emir; Kucukzeybek, Yuksel; Varol, Umut; Tarhan, Mustafa Oktay; Karaca, Burcak; Uslu, RuchanPurpose: Thymoquinone (TQ), an active ingredient of black seed oil (Nigella Sativa), has been shown to possess cytotoxic activity against a variety of cancer cell lines. Our purpose was to investigate if the cytotoxic and apoptotic effect of zoledronic acid (ZA) can be enhanced by the addition of the TQ in hormone- and drug-refractory prostate cancer cells PC-3 and DU-145. Methods: XTT cell proliferation assay was used to assess cytotoxicity; DNA fragmentation and caspase 3/7 activity were also measured. Results: The combination of TQ and ZA resulted in a significant synergistic cytotoxic activity and DNA fragmentation when compared to any single agent alone, in a dose- and time-dependent manner. In addition, TQ and ZA combination increased the caspase 3/7 activity in PC-3 cell line, while this activity could not be demonstrated in DU-145 cell line. Conclusion: TQ and ZA had minimal hematological and non-hematological toxicity profile compared to cytotoxic agents. So, this combination may be an alternative approach for patients who are unable to be treated by conventional treatments because of poor performance status.Öğe Gastric cancer with diffuse hepatic metastases and complete radiological response to triplet chemotherapy(Zerbinis Medical Publ, 2014) Varol, Umut; Alacacioglu, Ahmet; Yildiz, Ibrahim; Kucukzeybek, Yuksel; Uslu, RuchanÖğe Hormone Receptor, HER2/NEU and EGFR Expression in Ovarian Carcinoma - is here a Prognostic Phenotype?(Asian Pacific Organization Cancer Prevention, 2014) Demir, Lutfiye; Yigit, Seyran; Sadullahoglu, Canan; Akyol, Murat; Cokmert, Suna; Kucukzeybek, Yuksel; Alacacioglu, Ahmet; Cakalagaoglu, Fulya; Tarhan, Mustafa OktayPurpose: We aimed to evaluate the effects of hormone receptor, HER2, and epidermal growth factor receptor (EGFR) expression on epithelial ovarian cancer (EOC) prognosis and investigate whether or not phenotypic subtypes might exist. Materials and Methods: The medical records of 82 patients who were diagnosed with EOC between 2003 and 2012 and treated by platinum-based chemotherapy were retrospectively evaluated. Expression of EGFR, oestrogen (ER), progesterone (PR), and cerbB2 (HER2) receptors were assessed immunohistochemically on paraffin-embedded tissues of these patients. Three phenotypic subtypes were defined according to ER, PR, and HER2 expression and associations of these with EGFR expression, clinicopathologic features, platinum sensitivity, and survival were investigated. Results: When we classified EOC patients into three subtypes, 63.4% had hormone receptor positive (HR(+)) (considering breast cancer subtypes, luminal A), 18.3% had triple negative, and 18.3% had HER2(+) disease. EGFR positivity was observed in 37 patients (45.1%) and was significantly more frequent with advanced disease (p=0.013). However, no significant association with other clinicopathologic features and platinum sensitivity was observed. HER2(+) patients had significantly poorer outcomes than HER2(-) counterparts (triple negative and HR positive patients) (p=0.019). Multivariate analysis demonstrated that the strongest risk factor for death was residual disease after primary surgery. Conclusions: Triple negative EOC may not be an aggressive phenotype as in breast cancer. The HER2 positive EOC has more aggressive behaviour compared to triple negative and HR(+) phenotypes. EGFR expression is more frequent in advanced tumours, but is not related with poorer outcome. Additional ovarian cancer molecular subtyping using gene expression analysis may provide more reliable data.Öğe Pegylated liposomal doxorubicin (PLD) in heavily pretreated epithelial ovarian cancer patients(Oxford Univ Press, 2006) Gorumlu, Gurbuz; Kucukzeybek, Yuksel; Karabulut, Bulent; Terek, Mustafa C.; Uslu, Ruchan; Sanli, Ulus A.; Akman, Levent; Ozsaran, Aydin; Dikmen, Yilmaz; Goker, ErdemÖğe Profiling of angiogenic cytokines produced by hormone- and drug-refractory prostate cancer cell lines, PC-3 and DU-145 before and after treatment with gossypol(John Libbey Eurotext Ltd, 2008) Karaca, Burcak; Kucukzeybek, Yuksel; Gorumlu, Gurbuz; Erten, Cigdem; Gul, Mustafa K.; Cengiz, Ercument; Atmaca, Harika; Uzunoglu, Selim; Sanli, Ulus A.; Karabulut, Bulent; Uslu, RuchanIn this study, we aimed to investigate the angiogenic cytokine profiles of hormone- and drug-refractory prostate carcinoma cell lines, PC-3 and DU-145. We also studied the effect of gossypol, a natural polyphenolic cotton-seed extract, on the angiogenic cytokine profile of these cell lines. XTT cell proliferation assay was used for the assessment of cytotoxicity. For apoptosis, both histone-DNA fragmentation by ELISA assay and caspase 3/7 activity measurement were used. Angiogenic cytokine profiles of supernatants from both cell lines, before and after treatment with gossypol, were investigated using the human angiogenesis antibody array I (R). It was shown that the two different hormone- and drug-resistant prostate cancer cell lines, PC-3 and DU-145, constitutively express some important angiogenic cytokines, which are known to regulate tumorigenicity and angiogenesis in hormone- refractory prostate cancer. However, PC-3 and DU-145 cells have distinct angiogenic cytokine profiles. In addition, these two cells lines respond differently to gossypol treatment in terms of cytotoxicity and angiogenic cytokine secretion. After treatment with 10 mu M of gossypol, there was a 1.5-fold decrease in angiogenin and IL-8 levels and a 1.7- and 1.8-fold decrease in ENA-78 and GRO-alpha levels respectively, in DU-145 cells. For PC-3 cells, there were 1.6- and 1.8-fold decreases in IL-8 and VEGF levels, respectively. We conclude that PC-3 and DU-145 cells secrete significant amounts of different angiogenic cytokines that may explain their aggressive nature and metastatic potential. Gossypol treatment affects angiogenic cytokine secretion from these two cell lines in a different manner. By expanding our knowledge of the heterogeneous biological behavior of these two cell lines, novel treatment approaches can be developed for the treatment of prostate cancer.Öğe Regulation of growth factors in hormone- and drug-resistant prostate cancer cells by synergistic combination of docetaxel and octreotide(Wiley, 2009) Erten, Cigdem; Karaca, Burcak; Kucukzeybek, Yuksel; Gorumlu, Gurbuz; Cengiz, Ercument; Gul, Mustafa K.; Atmaca, Harika; Uzunoglu, Selim; Karabulut, Bulent; Sanli, Ulus A.; Uslu, RuchanOBJECTIVE To evaluate the effects of combined treatment with docetaxel and octreotide, a somatostatin analogue, on human hormone- and drug-refractory prostate cancer cell lines, PC-3 and DU-145, and on some growth factors related to tumour growth and angiogenesis in prostate cancer. MATERIALS AND METHODS A cell proliferation assay was used to assess the cytotoxicity of the drugs. To verify apoptosis, both DNA fragmentation (by enzyme-linked immunosorbent assay) and caspase 3/7 activity were measured. We also investigated the effect of combined docetaxel and octreotide on growth factors secreted from prostate cancer cells using a human growth factor antibody array. RESULTS The combination of docetaxel and octreotide resulted in significant synergistic cytotoxic activity and apoptosis, which was dose- and time-dependent. The combined treatment also resulted in significantly less secretion of stem cell factor and platelet-derived growth factor-AB in PC-3 cells, and transforming growth factor-beta and basic fibroblast growth factor in DU-145 cells, than in untreated controls. CONCLUSION Octreotide, a somatostatin analogue, combined with docetaxel might provide a rationale treatment option for hormone-refractory prostate cancer cells, not only by direct inhibition of cell proliferation but also by inhibiting the secretion of growth factors.Öğe Regulation of growth factors in hormone- and drug-resistant prostate cancer cells by synergistic combination of docetaxel and octreotide(Wiley, 2009) Erten, Cigdem; Karaca, Burcak; Kucukzeybek, Yuksel; Gorumlu, Gurbuz; Cengiz, Ercument; Gul, Mustafa K.; Atmaca, Harika; Uzunoglu, Selim; Karabulut, Bulent; Sanli, Ulus A.; Uslu, RuchanOBJECTIVE To evaluate the effects of combined treatment with docetaxel and octreotide, a somatostatin analogue, on human hormone- and drug-refractory prostate cancer cell lines, PC-3 and DU-145, and on some growth factors related to tumour growth and angiogenesis in prostate cancer. MATERIALS AND METHODS A cell proliferation assay was used to assess the cytotoxicity of the drugs. To verify apoptosis, both DNA fragmentation (by enzyme-linked immunosorbent assay) and caspase 3/7 activity were measured. We also investigated the effect of combined docetaxel and octreotide on growth factors secreted from prostate cancer cells using a human growth factor antibody array. RESULTS The combination of docetaxel and octreotide resulted in significant synergistic cytotoxic activity and apoptosis, which was dose- and time-dependent. The combined treatment also resulted in significantly less secretion of stem cell factor and platelet-derived growth factor-AB in PC-3 cells, and transforming growth factor-beta and basic fibroblast growth factor in DU-145 cells, than in untreated controls. CONCLUSION Octreotide, a somatostatin analogue, combined with docetaxel might provide a rationale treatment option for hormone-refractory prostate cancer cells, not only by direct inhibition of cell proliferation but also by inhibiting the secretion of growth factors.Öğe Second-Line Capecitabine and Oxaliplatin Combination for Gemcitabine-Resistant Advanced Pancreatic Cancer(Asian Pacific Organization Cancer Prevention, 2014) Bayoglu, Ibrahim Vedat; Varol, Umut; Yildiz, Ibrahim; Muslu, Ugur; Alacacioglu, Ahmet; Kucukzeybek, Yuksel; Akyol, Murat; Demir, Lutfiye; Dirican, Ahmet; Cokmert, Suna; Yildiz, Yasar; Karabulut, Bulent; Uslu, Ruchan; Tarhan, Mustafa OktayBackground: The role of second-line therapy in metastatic pancreatic cancer is not clear. In this study, we aimed to explore the second-line efficiency of capecitabine and oxaliplatin (XELOX) in patients with advanced pancreatic cancer who have received gemcitabine-based first-line therapy. Materials and Methods: We retrospectively evaluated 47 patients with locally advanced or metastatic pancreatic cancer previously treated with gemcitabine-based first-line regimens. Treatment consisted of oxaliplatin 130 mg/m(2) and capecitabine 1000 mg/m2 twice daily with a 3 week interval, until unacceptable toxicity or disease progression. Results: Median number of cycles was 4 (range, 2-10). The overall disease control rate was 38.3%. The median overall survival and progression-free survival from the start of second-line therapy were 23 weeks (95% CI: 16.6-29.5 weeks) and 12 weeks (95% CI: 9.8-14.4 weeks), respectively. The most common grade 3-4 toxicities were nausea, vomiting and hematologic side effects. Conclusions: Our result suggests that the combination of capecitabine and oxaliplatin was tolerated with manageable toxicity and showed encouraging activity as second-line treatment of advanced or metastatic pancreatic cancer patients with ECOG performance status 0-2.Öğe Trastuzumab Induced Maculopapular Skin Reactions Localized on the Left Forearm and Arm: A Case Report(Ortadogu Ad Pres & Publ Co, 2009) Kucukzeybek, Yuksel; Gorumlu, Gurbuz; Karaca, Saziye Burcak; Kazandi, Ali Can; Karabulut, Bulent; Uslu, Ruchan; Sanli, Ulus Ali; Goker, ErdemTrastuzumab, a monoclonal antibody targeting the extracellular domain of the HER 2 protein, either alone or in combination with chemotherapy, improves the outcome of women with early and metastatic breast cancer. Adverse events including cardiac dysfunction and infusion reactions may develop during trastuzumab therapy. However, skin toxicities are infrequent. We described a 57-year-old woman who was treated with trastuzumab for metastatic breast cancer. Due to the peripheral vein problems experienced by the patient, an implanted central venous access port was placed for the trastuzumab treatment by accessing the left subclavian vein with the distal tip in the mid-superior vena cava. The unusual finding appearing after trastuzumab treatment was the maculopapular rash, which was limited to the left arm and forearm. The patient underwent skin biopsy and pathological examination of specimen showed fixed drug eruptions. We reported this case because drug eruptions due to the trastuzumab treatment are rare and the lesion was only localized to the left arm and forearm of the mastectomy side and port catheter.Öğe Trastuzumab Induced Maculopapular Skin Reactions Localized on the Left Forearm and Arm: A Case Report(Ortadogu Ad Pres & Publ Co, 2009) Kucukzeybek, Yuksel; Gorumlu, Gurbuz; Karaca, Saziye Burcak; Kazandi, Ali Can; Karabulut, Bulent; Uslu, Ruchan; Sanli, Ulus Ali; Goker, ErdemTrastuzumab, a monoclonal antibody targeting the extracellular domain of the HER 2 protein, either alone or in combination with chemotherapy, improves the outcome of women with early and metastatic breast cancer. Adverse events including cardiac dysfunction and infusion reactions may develop during trastuzumab therapy. However, skin toxicities are infrequent. We described a 57-year-old woman who was treated with trastuzumab for metastatic breast cancer. Due to the peripheral vein problems experienced by the patient, an implanted central venous access port was placed for the trastuzumab treatment by accessing the left subclavian vein with the distal tip in the mid-superior vena cava. The unusual finding appearing after trastuzumab treatment was the maculopapular rash, which was limited to the left arm and forearm. The patient underwent skin biopsy and pathological examination of specimen showed fixed drug eruptions. We reported this case because drug eruptions due to the trastuzumab treatment are rare and the lesion was only localized to the left arm and forearm of the mastectomy side and port catheter.
